KR20050004394A - New process for producing diphenylsulfone compounds - Google Patents

Abstract

PURPOSE: A process for preparing a diphenylsulfone compound is provided to easily separate out by-products and unreacted biphenylsulfone compound from a salt of object compound by using an mixed solvent of water and tolunene and by pulverization. CONSTITUTION: The diphenylsulfone compound of the formula 1 is prepared by the process comprising reacting 4,4'-dihydroxydiphenylsulfone compound of the formula 2 with an isopropyl halide of the formula 3: R-X in the presence of a reaction solvent and a base, wherein the process comprises depositing a salt of object compound of the formula 4 in a form of solid by using a mixed solvent of water and toluene as the reaction solvent, followed by filtrating to separate out unreacted 4,4-dihydroxydiphenylsulfone compound and a by-product, diether compound of the formula 5 simultaneously, provided that water is employed in an amount of 0.25-3 parts by weight, with respect to 1 parts by weight of 4,4-dihydroxydiphenylsulfone and the filtrated salt of object compound is treated with an acid upon pulverizing. In the formulas 1-5, R represents isopropyl, X represents a halogen atom, and M represents an alkali metal or an alkali earth metal.

Description

New process for producing diphenylsulfone compounds

The present invention relates to a method for preparing a diphenylsulfone compound represented by the following formula (1) and useful as a developer of a white pigment (Leuco dye) used in thermal recording paper.

Formula 1

In the formula, R represents an isopropyl group.

Method for producing a diphenyl sulfone compound containing a compound represented by the formula (1) is Japanese Patent Laid-Open No. 58-20493, 58-82788, 60-13852, 60-56949, Japanese Patent Publication No. 4-210995 , International Patent Publication No. 84/02882, International Patent Publication No. 91/11433, Japanese Patent Publication No. 2001-261633, Korean Patent Publication No. 2002-0005619, Korean Patent Publication No. 2002-0091140, etc. The presence of polar solvent or water solvent such as dimethylformamide or dimethyl sulfoxide and alcohol using 4,4'-dihydroxydiphenylsulfone compound represented by the following formula (2) and halogenated alkyl represented by the following formula (3) as raw materials It is a method of making it react under.

Formula 2

Formula 3

R-X

In the above formula, R represents an isopropyl group, and X represents a halogen element.

As such, when the 4,4'-dihydroxydiphenylsulfone compound and the halogenated alkyl are reacted in the presence of a solvent and a base, the reaction solution includes not only the 4-hydroxy-4'-isopropoxydiphenylsulfone compound as the target compound. Unreacted 4,4'-dihydroxydiphenylsulfone compound (hereinafter referred to simply as BPS) and by-product 4,4'-diisopropoxydiphenylsulfone represented by the following formula (5) Since the compound is mixed, it is very important to effectively separate the target compound with high purity from these unreacted substances and by-products.

Formula 5

In the formula, R represents an isopropyl group.

To this end, Japanese Patent Application Laid-Open No. 3-258760 extracts these two compounds from the aqueous layer by using an organic solvent to separate BPS mixed with the target compound 4-alkoxy-4'-hydroxydiphenylsulfone compound. And a method of separating an alkali metal salt of BPS by moving it to an aqueous layer through pH adjustment using an aqueous solution of hydrogen carbonate or the like.

Japanese Patent Laid-Open No. 5-255234 discloses a method in which an alkyl halide is added to a two-phase solvent system of an alkaline aqueous solution in which BPS is dissolved and a toluene solvent, and an alkaline substance is added to maintain the pH at 7.5 to 9.5. In this method, when the reaction is terminated and the layers are separated, the salt of the unreacted BPS is the aqueous layer, and the salt and the diether of the 4-alkoxy-4'-hydroxydiphenylsulfone compound represented by the following Chemical Formula 4 The toluene layer is separated and crystallized separately to explain that only 4-alkoxy-4'-hydroxydiphenylsulfone compound as the target compound is obtained as a solid. However, the salt compound of 4-alkoxy-4'-hydroxydiphenylsulfone represented by the general formula (4) is not only difficult to dissolve in a nonpolar organic solvent such as toluene, but also has a separate pH control operation, that is, 4-alkoxy-4 ' 4-Alkoxy-4 when cooled and crystallized, unless neutral pH adjustment is performed to convert the salt compound of hydroxydiphenylsulfone to 4-alkoxy-4'-hydroxydiphenylsulfone compound Since a salt compound of '-hydroxydiphenylsulfone was obtained, there was a problem contrary to the object of the invention.

Formula 4

In the formula, R is an isopropyl group, M represents an alkali metal or alkaline earth metal.

On the other hand, Korean Patent Laid-Open Publication No. 2002-0091140 is a method for separating the BPS mixed with the 4-alkoxy-4'-hydroxydiphenylsulfone compound, by adjusting the aqueous solution containing these compounds to pH 8.4 ~ 8.7, organic A method of adjusting the pH of an aqueous layer to a range of pH 8.3 to 8.6 for organic layer separation by extracting with a solvent, separating the organic layer and the aqueous layer, and then adding water or water adjusted to a fixed pH value to the separated organic layer is disclosed. .

In the above production methods, an unreacted BPS is usually separated using an expensive organic solvent, and the by-produced diether compound is extracted and separated into an organic solvent through a separate process, or crystallized or recrystallized. The separation method is not only economical, but also has long and complicated disadvantages.

Accordingly, the present inventors are seeking a method for improving the conversion rate in post-treatment of the salt compound of the target compound while being able to easily separate the salt compound of the target compound and unreacted BPS and by-products generated during the reaction. When using a mixed solvent of water and toluene as a reaction solvent and acid-treating the salt compound of the target compound obtained, water was ground to adjust the pH to neutral to easily precipitate the salt compound represented by the above formula (4) in a solid state. It is possible to separate the unreacted BPS and the by-produced diether compound at the same time only by filtration and to convert the solid salt compound into the target compound by pulverization without performing layer separation or the like to obtain through filtration. The present invention has been completed.

Accordingly, an object of the present invention is to facilitate the precipitation of a salt compound of a target compound by using a mixed solvent of water and toluene as a reaction solvent, and to separate it from the unreacted BPS and by-products only by filtering the salt. The salt of the desired compound can be converted through pulverization and obtained by filtration, which provides a method for preparing a diphenylsulfone compound.

Method for producing a diphenyl sulfone compound represented by the formula (1) to achieve the above object is 4,4'- dihydroxy diphenyl sulfone compound represented by the formula (2) and isopropyl halogen represented by the formula (3) It includes reacting the cargo in the presence of a reaction solvent and a base, using a mixed solvent of water and toluene as a reaction solvent to precipitate a salt compound of the target compound represented by the following formula (4) as a solid to filter the unreacted 4,4 The '-dihydroxydiphenyl sulfone compound and the by-produced diether compound represented by the formula (5) are separated at the same time, and the salt compound of the target compound represented by the following formula (4) with acid treatment accompanied by grinding do.

Formula 4

In the formula, R is an isopropyl group, M represents an alkali metal or alkaline earth metal.

The present invention will be described in more detail as follows.

As in the present invention, when BPS represented by Chemical Formula 2 and isopropyl halide represented by Chemical Formula 3 are reacted in the presence of a base using a predetermined amount of a two-phase mixed solvent of water and toluene as a solvent, As soon as the resulting 4-hydroxy-4'-isopropoxydiphenylsulfon salt compound is formed, it is precipitated in the reaction solution in solid form.

In order for the salt compound of the target compound to be present in the solid state almost immediately, the amount of water in the reaction solvent is used in an amount of 0.25 to 3.0 parts by weight, preferably 0.5 to 1.5 parts by weight based on 1 part by weight of the BPS compound as a raw material. Good to do. If the amount of water in the reaction solvent is less than 0.25 parts by weight based on 1 part by weight of the BPS compound, the reaction proceeds as a result of the solid precipitated as the reaction proceeds, and as a result, the reaction time becomes very long and the reaction conversion rate is very low. A problem arises. On the other hand, when it is used more than 3.0 parts by weight, the proportion of the salt compound of the target compound produced by the reaction precipitates in solid form is drastically reduced to 50% or less and a considerable amount is dissolved in the reaction solution, making it difficult to achieve the object of the present invention. do.

When toluene is used together with water as a reaction solvent in the present invention, toluene dissolves the diether represented by Formula 5, which is produced as a by-product during the reaction, and 4-hydroxy-4'- represented by Formula 4 above. When the isopropoxydiphenylsulfone salt compound is filtered, the diether is separated with the salt of BPS dissolved in the aqueous layer as a filtrate, so that only 4-hydroxy-4'-isopropoxydiphenylsulfone salt of high purity is obtained by filtration alone. It serves to obtain the compound as a solid.

As described above, Japanese Patent Application Laid-open No. Hei 5-255234 has an example of using a two-phase solvent of water and toluene, but here, the 4-hydroxy-4'-isopropoxydiphenylsulfone salt compound produced by reaction is extracted. Toluene is used for the purpose. Therefore, the purpose and technique are different from those in which a mixed solvent of water and toluene is used as the reaction solvent as in the present invention. That is, in the present invention, toluene is used as the reaction solvent to dissolve the by-produced diether compound in the reaction solution to simultaneously separate the salt with unreacted BPS.

Of course, 4-hydroxy is a by-produced diether compound using a non-water-miscible organic solvent such as toluene in the reaction solution after completion of the reaction, without using a mixed solvent of water and toluene as a reaction solvent as in the present invention. It can also isolate | separate by filtering with -4'-isopropoxydiphenyl sulfone salt compound. However, since the diether compound remains unwashed in the 4-hydroxy-4'-isopropoxydiphenylsulfone salt compound which precipitates during the reaction as solid particles, the method is simple, but the high purity of the target compound There is a problem in manufacturing.

The amount of toluene which plays a role as described above is preferably used so as to be 0.05 to 1.0 parts by weight, preferably 0.1 to 0.5 parts by weight, relative to 1 part by weight of BPS. If it is less than 0.05 part by weight, the diether compound cannot be sufficiently removed, and if it is usually used within 0.5 part by weight and more than 1.0 part by weight, the economic efficiency will be reduced.

Bases used for the reaction are usually alkali metal hydroxides such as sodium hydroxide, potassium hydroxide; Alkaline earth metal hydroxides, for example, magnesium hydroxide, calcium hydroxide and the like, and the amount is preferably 2.0 to 3.0 molar ratio, preferably 2.0 to 2.5 molar ratio with respect to 1 mole of BPS as a raw material. When the amount of base is used in a 2.0 to 3.0 molar ratio, the BPS dichloride compound is completely dissolved in water, which is a solvent, and the reaction starts. The base is dissolved in water even after the reaction is completed. When used less than 2.0 molar ratio, some of the BPS monochloride compound is not dissolved in water as a reaction solvent, so that the reaction does not proceed well, and the salt represented by the formula (3) is produced because the solid is maintained after the reaction is completed. It is difficult to separate by the filtration method to achieve the present invention by mixing with the compound occurs.

In order to solve this problem, after completion of the reaction, an appropriate amount of base can be added to convert the BPS monochloride compound into a BPS dichloride compound so that it can be completely dissolved in the reaction solution. However, a large amount of base must be additionally used. Due to the high pH of the reaction solution there is a problem that a significant amount of the salt compound represented by the formula (4) to be precipitated as a solid is dissolved in the reaction solution.

The temperature of the reaction is preferably carried out at 40 ~ 150 ℃, preferably in the range of 50 ~ 90 ℃.

After the reaction is completed, the reaction solution is cooled to room temperature to obtain a salt compound of 4-hydroxy-4'-isopropoxydiphenylsulfone in a solid state. The reaction solution can be diluted by adding an arbitrary amount of water so that the precipitated solid 4-hydroxy-4'-isopropoxydiphenylsulfone salt compound (Formula 4) can be easily filtered. There is no limit to the quantity.

The filtered solid is washed sequentially with water and toluene to wash away the BPS dichloride compound and the diether compound represented by Chemical Formula 5.

The BPS dichloride compound separated into the filtrate is treated with an acid such as hydrochloric acid or sulfuric acid to adjust the pH to neutral or less, and precipitates as a solid, which can be easily recovered and reused as BPS.

The method for preparing 4-hydroxy-4'-isopropoxydiphenyl sulfone compound as a target compound from the 4-hydroxy-4'-isopropoxydiphenyl sulfone salt compound separated by the above method is as follows;

First, the solid separated by filtration is released into water, and the pH of the mixed solution is adjusted to neutral by adding an acid such as hydrochloric acid or sulfuric acid with grinding. In this case, the acid may be added before grinding or may be appropriately divided while grinding, and the method is not limited.

The grinding method can be selected and used from any type of grinding method, such as a milling method such as a ball mill, a grinding method using a homogenizer, a wet grinding method using a grinder, or a grinding method using a mixer.

When acid treatment of the aqueous dispersion of the 4-hydroxy4'-isopropoxydiphenylsulfone salt compound represented by the formula (4) involves pulverization, the reaction efficiency of the salt and the acid is increased through pulverization, and only the pulverization is used as the target compound. The conversion of to obtain a solid compound of the target compound.

When the reaction conversion is completed, the pH is adjusted to neutral. At this time, the target compound in the solid state is filtered, washed with water, and dried to obtain the target compound. If the particle size is small and there is a problem in filtration, the dispersion is heated to 40 to 100 ° C. while stirring, and then stirred for 1 to 12 hours before cooling to increase the size of the solid particles, thereby solving the problem of filtration. have.

Hereinafter, preferred examples are provided to help understanding of the present invention, but the following examples are merely to illustrate the present invention, and the scope of the present invention is not limited to the following examples.

Example 1: Preparation of 4-hydroxy-4'-isopropoxydiphenyl sulfone (Compound 1 compound) as a target compound

(1) 250 g of water, 50 g of toluene, and 117.6 g (2.1 mole) of potassium hydroxide were added to a 2 L flask, followed by 250 g (1.0 mole) of BPS, followed by stirring to dissolve completely. The internal temperature was adjusted to 70-80 ° C. and then 184.5 g of isopropyl bromide was added dropwise over 12 hours. After the addition was completed, the same temperature range was maintained for 6 hours, and then the reaction solution was cooled to room temperature. A small amount of the reaction solution was adjusted to neutral pH with concentrated hydrochloric acid, followed by HPLC analysis of the extracted organic layer with a small amount of ethyl acetate. The area percentage was 17.2% of the raw material BPS, 79.1% of the target compound, and the byproduct. Dieter was 3.2% and other byproducts were 0.5%. At this time, HPLC was used for Waters 510 model, the UV absorption wavelength of the detector was 262 nm, Analytical column was used Nova-Pak C18 of Waters, and acetonitrile / phosphoric acid was used as the developing solvent by volume ratio of 60: 40: 0.1 It was used as a mixed solvent.

(2) 100 g of water was added to the reaction solution, and the solid was filtered. The filtered solid was washed with 250 g of water and 100 g of toluene. A small amount of this solid was taken, dried and dissolved in a developing solvent, and analyzed by HPLC under the above conditions. The results were area percent, 99.23% for the target compound, 0.25% for BPS, 0.02% for diether, and 0.5% for other byproducts.

In addition, a small amount of the filtrate was adjusted to neutral pH with concentrated hydrochloric acid, extracted with a small amount of ethyl acetate, and the organic layer was analyzed by HPLC under the same conditions. And other byproducts were analyzed at 0.3%.

(3) Subsequently, the filtered solid was placed in 250 g of water, a homogenizer (IKA model model Ultraax T50 basic) was installed, 85 g of concentrated hydrochloric acid was added, and the solid particles were pulverized at 5,000 rpm for 6 hours. After pH adjustment was completed, the mixture was cooled to room temperature and the solid was filtered. The filtered solid was washed with 500 g of water and dried to obtain 219.3 g of the target compound. As a result of analyzing the dried target compound by the same HPLC, 99.76% of the target compound as an area percent, 0.03% of unreacted BPS, 0.06% of by-product diether and 0.15% of other byproducts were analyzed.

Meanwhile, the filtrate was collected and concentrated pH was adjusted to neutral hydrochloric acid, followed by stirring at room temperature for 2 hours, followed by filtration to obtain 38 g of solid. The result was analyzed by HPLC under the same conditions, and BPS 97.60% as the target compound. This was analyzed as 1.9%, dieter 0.30%, and other byproducts 0.20%.

Example 2: Preparation of 4-hydroxy-4'-isopropoxydiphenyl sulfone (Compound 1 compound) as a target compound

(1) 250 g of water, 12.5 g of toluene and 117.6 g (2.1 mole) of potassium hydroxide were added to a 2 L flask, followed by 250 g (1.0 mole) of BPS, followed by stirring to dissolve completely. The internal temperature was adjusted to 70-80 ° C. and 184.5 g (1.5 mole) of isopropyl bromide was added dropwise over 12 hours. After the addition was completed, the same temperature range was maintained for 6 hours, and then the reaction solution was cooled to room temperature. A small amount of the reaction solution was adjusted to neutral pH with concentrated hydrochloric acid, and then extracted with a small amount of ethyl acetate. The extracted organic layer was analyzed by the same HPLC as in Example 1, where the area percentage was 15.8% of the raw material BPS, and the target compound was obtained. 80.0%, by-product diether 3.7%, and other byproducts 0.5%.

(2) 100 g of water was added to the reaction solution, and the solid was filtered. The filtered solid was washed with 250 g of water and 100 g of toluene.

(3) Subsequently, the filtered solid was treated in the same manner as in Example 1 to obtain 216.2 g of the target compound. HPLC analysis of the target compound showed 99.53% as area percent, 0.04% as unreacted BPS, 0.21% as dietary byproduct, and 0.22% as other byproducts.

Example 3: Preparation of 4-hydroxy-4'-isopropoxydiphenyl sulfone (Compound 1 compound) as a target compound

(1) 750 g of water and 75 g of toluene were reacted in the same manner as in Example 1, and then the reaction solution was analyzed by HPLC. As a result, the area percentage was 33.6% of the raw material BPS, 59.3% of the target compound, and by-products. Phosphorus diether was 6.8% and other byproducts were 0.3%.

(2) and (3) The same procedure as in Example 1 was carried out to obtain 160.1 g of the target compound. As a result of analyzing the target compound by HPLC, 99.57% as area percentage, 0.15% as unreacted BPS, 0.08% as dietary byproduct, and 0.00% as other byproducts.

Comparative Example 1

62 g of water, 50 g of toluene, and 117.6 g (2.1 mole) of potassium hydroxide were added to a 2 L flask, followed by 250 g (1.0 mole) of BPS, followed by stirring to completely dissolve it. The internal temperature was adjusted to 70-80 ° C., and 184.5 g (1.5 mole) of isopropyl bromide was added little by little. After 6 hours, the reaction solution was filled with a solid and stirring was impossible, so that the reaction could not be performed anymore.

Comparative Example 2

450 g of BPS, 255 ml of 48% aqueous sodium hydroxide solution and 120 ml of water were placed in a reaction tank and mixed under stirring while raising the temperature to 75 ° C. 225 g of isopropyl bromide was continuously stirred at 55 ± 5 ° C. for a total of 20 hours from the start of dropping. 235 ml of warm water was added to the reaction solution, and heated at 80 ° C. for 1 hour to remove unreacted isopropyl bromide by evaporation.

Then, 300 ml of warm water and 250 ml of toluene were added at 80 ° C. and sufficiently stirred. The aqueous layer was separated. To the obtained aqueous layer, 1,100 ml of toluene and 200 ml of water were added at 79 DEG C, and stirred for 30 minutes at the same temperature. In addition, 30% dilute sulfuric acid was added dropwise little by little with stirring at 82 ° C. for 1 hour to uniformly adjust the pH of the aqueous layer of the reaction solution to 8.4-8.7. The resulting solution was left at 82 ° C. for 30 minutes and the toluene layer was separated. To the obtained toluene layer, 300 ml of toluene and 300 ml of water were added at 82 DEG C, and 30% dilute sulfuric acid was added dropwise little by little under stirring at 82 DEG C to adjust the pH of the aqueous layer uniformly to 8.3 to 8.6. The resulting solution was left at 82 ° C. for 30 minutes and the toluene layer was separated. 250 ml of water was added to the toluene layer at 82 ° C. and stirred at the same temperature for 2 hours. The solution obtained was then left at 82 ° C. for 30 minutes and the toluene layer was separated. The toluene layer obtained was cooled to deposit crystals. The crystals were separated by filtration, washed with toluene and dried to obtain 350 g of 4-isopropoxy-4'-hydroxydiphenylsulfone as a target compound as a powder.

HPLC analysis of the product showed that the target compound was 97.8 area%, diether 1.83 area%, BPS 0.23 area%, and other byproducts 0.14 area%.

As described above in detail, according to the present invention, BPS and isopropyl halides are reacted in the presence of a two-phase mixed solvent of water and toluene and a base to obtain a salt of the target compound, followed by acid treatment with pulverization. When preparing the diphenyl sulfone compound represented by 1, alkali or alkaline earth metal salt compound of 4-hydroxy-4'-isopropoxydiphenyl sulfone is precipitated as a solid in the reaction solution, and this solid compound is simply filtered. The reaction raw material BPS and the by-product diether compound can be easily separated, and the salt of the filtered target compound is dispersed and acid treated with pulverization to obtain the target compound with improved conversion. Can be obtained through filtration, and the separation of the layers by performing a difficult pH control while using an expensive organic solvent A very simple method by which not only more economical but also be readily applied on an industrial scale than the process of separating the conventional complicated production process can be repeated at least once.

Claims (6)

The 4,4'-dihydroxydiphenyl sulfone compound represented by the following formula (2) and the isopropyl halide represented by the following formula (3) are reacted in the presence of a reaction solvent and a base to prepare a diphenyl sulfone compound represented by the following formula (1) In the way, By using a mixed solvent of water and toluene as the reaction solvent to precipitate a salt compound of the target compound represented by the following formula (4) as a solid to filter the unreacted 4,4'-dihydroxydiphenyl sulfone compound and the following formula (5) Simultaneously separate the by-produced diether compound to be expressed, except that water is used to 0.25 to 3 parts by weight based on 1 part by weight of 4,4'-dihydroxydiphenyl sulfone, and the filtered salt compound of the target compound A method for producing a diphenylsulfone compound, characterized in that the acid treatment is accompanied by grinding. Formula 1 In the formula, R represents an isopropyl group. Formula 2 Formula 3 R-X In the above formula, R represents an isopropyl group, and X represents a halogen element. Formula 4 In the formula, R is an isopropyl group, M represents an alkali metal or alkaline earth metal. Formula 5 In the formula, R represents an isopropyl group. The method for producing a diphenyl sulfone compound according to claim 1, wherein toluene is used in an amount of 0.05 to 1.0 parts by weight based on 1 part by weight of 4,4'-dihydroxydiphenyl sulfone. The method for producing a diphenyl sulfone compound according to claim 1, wherein an alkali metal hydroxide or an alkaline earth metal hydroxide is used as the base. The method for producing a diphenyl sulfone compound according to claim 1 or 3, wherein the base is used in an amount of 2.0 to 3.0 molar ratio with respect to 1 mol of 4,4'-dihydroxydiphenyl sulfone. The method of claim 1, further comprising: cooling the reaction solution to room temperature after the reaction is completed to precipitate a solid including the 4-hydroxy-4'-isopropoxydiphenylsulfone salt compound represented by Chemical Formula 3; Filtering the precipitated solid to separate the di-chloride compound of 4,4'-dihydroxydiphenylsulfone compound and the diether compound represented by Formula 5; Acid treatment of the dichloride salt of the 4,4'-dihydroxydiphenylsulfone compound separated by the filtrate to adjust the pH below neutral to precipitate as a solid to recover the unreacted 4,4'-dihydroxydiphenylsulfone compound. step; Separately, the filtered solid is put in water and acid treatment with pulverization to adjust the pH to neutral to convert the target compound into a solid state; And After the pH is adjusted to neutral, the method for producing a diphenylsulfone compound comprising the step of filtering the target compound in the solid state, washing with water, and drying. The method for producing a diphenylsulfone compound according to claim 1 or 5, wherein the grinding is accompanied before or after the addition of acid.